Usher syndrome research summary from Dr Mariya Moosajee

Dr Mariya Moosajee is a Consultant Ophthalmologist at Moorfields Eye Hospital and Great Ormond Street Hospital for Children in London. She specialises in genetic eye disease such as Usher syndrome. She leads an active research team at UCL Institute of Ophthalmology, London, where she is undertaking several projects related to Usher syndrome in the hope to develop a potential treatment that may be applicable in the future for patients and their families. Here is a summary of her projects:

1. Developing small molecule drugs that can treat a subset of Usher syndrome patients

Approximately 30% of genetic mutations in Usher syndrome are due to an abnormal stop signal being introduced in the gene (this is called a nonsense mutation). When your cells try to read your gene, if it encounters this premature stop signal it will stop making the required protein, and this loss of function leads to Usher syndrome. There are now a group of drugs that can bind to your protein-making machinery in your cells and override the abnormal stop signals leading to the formation of normal full length functioning protein. This can restore between 20-25% levels of normal protein and this may be enough to halt or slow the retinal degeneration seen in Usher syndrome. This work has been published in the scientific literature and we are now trying to translate this therapy to patients. To learn more, please visit: https://vimeo.com/199657263. We are trying to raise the funding to move into a clinical trial. Please watch this space, for updates on our progress. If you are keen to check what type of mutation you have causing your usher syndrome, please send Dr Moosajee an email (contact details below) with your genetic report so she can advise you on whether this treatment would be suitable for you.

Small molecule drugs only works on a subset of patients with a particular mutation. The gene USH2A is the commonest cause of Usher syndrome type 2 and contributes to the majority of Usher syndrome cases overall. Mutations in this gene can also cause retinitis pigmentosa without any hearing problems. The gene is very large and extends over 19,000 kilobases (or letters of the genetic code). Unfortunately, conventional viral gene therapy vectors can only accommodate genes that are smaller than 9000 kilobases. So we need to find an alternative form of gene delivery for USH2A. My team is developing a non-viral gene delivery system which can hold large genes, including USH2A, and testing its safety and effectivity in Usher disease models. This includes (i) a zebrafish model with an ush2a genetic change generated through gene editing, and (ii) human retinal models from patients own skin samples, which are reprogrammed to stem cells and then differentiated into early eye cups growing in a dish. To learn more about this stem cell technology watch this animation: https://vimeo.com/227432768. This project is still in the preclinical phase and will last 3 years. We will keep you updated on the progress.

At Moorfields Eye Hospital we have a state-of-the-art Clinical Research Facility with high-tech imaging equipment that enables us to study the detailed clinical features of Usher syndrome and monitor disease progression. My team are making advances in our understanding of the relationship between the genetic diagnosis and the clinical features, providing insights into disease mechanisms and potential therapeutic targets. We are also trying to establish the clinical tests which can measure a true change in the condition over a fixed period of time, so when we move to clinical trials, we will know what measures portray an accurate response to treatment.

Mariya works closely with Prof Andrew Webster and Dr Adam Dubis at Moorfields Eye Hospital and Dr Richard Harbottle at the German Cancer Research Center, Heidelberg. Here is a joint summary of ongoing research that may be helpful for Usher patients: https://vimeo.com/238404158.

If you are keen to learn more about Mariya's research or want to take part, please email her directly on or call her research coordinator, Samantha Lawrence on tel: 0207 566 2265 or email .

Exciting Usher Research Projects

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